Cool Prime Comparative Effectiveness Study for Mild HIE

NCT04621279 | Recruiting DMC

• 1 other identifier: STU-2022-0714
• Study Type: observational
• Target: 460
• Locations: 1 country
• Sites: 1

Brief Summary

To determine effectiveness of therapy to improve neurodevelopmental outcomes in infants with mild HIE. To determine the adverse effects of Therapeutic Hypothermia (TH) in mild HIE on the neonate and his/her family. Determine heterogeneity of the treatment effect across key subgroups obtained in the first 6 hours after birth prior to the decision to initiate therapy.

Conditions

Mild Hypoxic Ischemic Encephalopathy of Newborn

Keywords

mild HIE (Hypoxic Ischemic Encephalopathy); neonatal encephalopathy; brain ischemia; brain hypoxia

Outcome Measures

Primary Outcomes (1)

• Effectiveness of normothermia in infants as measured by Composite Bayley IV score

  Effectiveness of normothermia in infants is measured by Composite Bayley IV score scale, which is. an extensive formal developmental assessment tool for diagnosing developmental delays in early childhood. Possible scores range from 55- 120 where lower scores indicate worse outcome.

  22-26 months of age.

Secondary Outcomes (4)

• Adverse events SAE

  Discharge (approximately 7 days)

• Parent-Infant stress and bonding as measured by MIBS

  3-4 months

• Parent-Infant stress and bonding as measured by IBQR

  3-4 months

• Parent-Infant stress and bonding as measured by PSI

  3-4 months

Other Outcomes (7)

• Infant neurological integrity as measured with HNNE

  Discharge

• Infant neurological integrity as measured with HINE

  3 - 4 months

• Infant neurological integrity as measured with HINE

  22-26 months

Study Arms (1)

Mild HIE

Mild HIE identified in the first 6 hours of life according to the published PRIME study definition: newborn with evidence of encephalopathy (using the validated Sarnat Exam) NOT meeting prior cooling trials criteria.

Procedure: Normothermia; Procedure: Whole body therapeutic hypothermia

Interventions

Normothermia PROCEDURE

Usual care for first 72 hours for neonates with mild encephalopathy maintaining core temperature (36.5°C ± 1 C).

Mild HIE

Whole body therapeutic hypothermia PROCEDURE

Whole-body therapeutic hypothermia (33.5°C ± 0.5°C) for 72 hours began by 6 hours of age for neonates with mild encephalopathy per site standard of care practice.

Mild HIE

Eligibility Criteria

• Age: 36 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Term infants ≥ 36 weeks' gestation with evidence of both perinatal event fetal acidosis and encephalopathy on exam.

You may qualify if:

• Neonates born at ≥ 36 0/7 weeks
• Mild Encephalopathy on neonatal neurologic exam within 6 hours after birth: defined as presence of at least 2 signs of mild, moderate, or severe encephalopathy with no more than 2 signs in the moderate or severe category.
• Perinatal Acidosis based on at least one of the following (A or B):
• pH ≤ 7.00 in any cord or first infant gas (arterial, venous, or capillary) within ≤ 60 min OR base deficit ≥ 16 in any cord or first infant gas (arterial, venous or capillary) within ≤ 60 min
• If pH is between 7.01 and 7.15, OR base deficit is between 10 and 15.9 mmol/liter, OR blood gas is not available, an acute perinatal event is an additional criteria required (see below definition)
• An acute perinatal event is defined by at least one of the following:
• Apgar score at 10 min ≤ 5
• Continued need for resuscitation at 10 min (chest compressions, bag mask ventilation, or positive pressure ventilation)
• Uterine rupture, placental abruption, cord accident (prolapse, rupture, knot or tight nuchal cord)
• maternal trauma, maternal hemorrhage, or cardiorespiratory arrest
• fetal exsanguination from either vasa previa or feto-maternal hemorrhage, shoulder dystocia
• Any evidence suggestive of acute perinatal event.
• Infants are still eligible for enrollment in the COOLPRIME study if the cord or infant's first blood gas (arterial, venous, or capillary) is obtained \>60 minutes of life.

You may not qualify if:

• Gestational age at birth \< 36 0/7 weeks
• Birth weight \< 1800gm
• Head circumference \<30cm
• Congenital or chromosomal anomaly associated with abnormal neurodevelopment or death
• Moderate or Severe HIE of 3 or more moderate or severe abnormalities on COOLPRIME Sarnat exam within 6 hours of life
• Any seizures within first six hours of life
• Redirection of care is being considered

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• University of California, San Francisco: collaborator
• Children's National Research Institute: collaborator
• Children's Hospital Los Angeles: collaborator
• St. Louis University: collaborator
• Stanford University: collaborator
• University of Utah: collaborator
• University of Pittsburgh Medical Center: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• University College Cork: collaborator
• The Children's Hospital of San Antonio: collaborator
• Harvard University: collaborator
• Washington University School of Medicine: collaborator
• Sharp HealthCare: collaborator
• The Cleveland Clinic: collaborator
• University of Florida Health: collaborator
• Emory University: collaborator
• Nationwide Children's Hospital: collaborator
• Children's Hospital of Orange County: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75208, United States

RECRUITING

Related Publications (4)

• Prempunpong C, Chalak LF, Garfinkle J, Shah B, Kalra V, Rollins N, Boyle R, Nguyen KA, Mir I, Pappas A, Montaldo P, Thayyil S, Sanchez PJ, Shankaran S, Laptook AR, Sant'Anna G. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol. 2018 Jan;38(1):80-85. doi: 10.1038/jp.2017.164. Epub 2017 Nov 2.

  PMID: 29095433 BACKGROUND

• Chalak LF, Nguyen KA, Prempunpong C, Heyne R, Thayyil S, Shankaran S, Laptook AR, Rollins N, Pappas A, Koclas L, Shah B, Montaldo P, Techasaensiri B, Sanchez PJ, Sant'Anna G. Prospective research in infants with mild encephalopathy identified in the first six hours of life: neurodevelopmental outcomes at 18-22 months. Pediatr Res. 2018 Dec;84(6):861-868. doi: 10.1038/s41390-018-0174-x. Epub 2018 Sep 13.

  PMID: 30250303 BACKGROUND

• Chalak LF, Adams-Huet B, Sant'Anna G. A Total Sarnat Score in Mild Hypoxic-ischemic Encephalopathy Can Detect Infants at Higher Risk of Disability. J Pediatr. 2019 Nov;214:217-221.e1. doi: 10.1016/j.jpeds.2019.06.026. Epub 2019 Jul 10.

  PMID: 31301853 BACKGROUND

• El-Dib M, Inder TE, Chalak LF, Massaro AN, Thoresen M, Gunn AJ. Should therapeutic hypothermia be offered to babies with mild neonatal encephalopathy in the first 6 h after birth? Pediatr Res. 2019 Mar;85(4):442-448. doi: 10.1038/s41390-019-0291-1. Epub 2019 Jan 16.

  PMID: 30733613 BACKGROUND

Related Links

• Study website page for participants.

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Brain Ischemia; Hypoxia, Brain

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Lina Chalak, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lina Chalak, MD

CONTACT

214-648-3903; lina.chalak@utsouthwestern.edu

Pollieanna Sepulveda, MSN, RN

CONTACT

214-648-3698; pollieanna.sepulveda@utsouthwestern.edu

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PROFESSOR

Study Record Dates

• First Submitted: October 23, 2020
• First Posted: November 9, 2020
• Study Start: July 19, 2023
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): January 1, 2029
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)